UTRECHT: MYELOMA IMMUNOTHERAPY

Immunotherapy of Myeloma and other haematological tumors printPrint Laat de tekst voorlezen met ReadSpeakerLees voor Immunotherapy of Myeloma and other haematological tumors Myeloma and several other haematological cancers can be treated by cellular immunotherapy, as illustrated by the success of allogeneic stem cell transplantation (allo-SCT) and donor lymphocyte infusions (DLI) to induce long term remissions in a fraction of patients. This donor T-cell-mediated therapeutic Graft-vs-Tumor effect (GvT) is, however, frequently inefficiently developed, compromised by several tumor microenvironment-related immune escape mechanisms and is furthermore associated with severe complications such as Graft-vs-Host Disease (GvHD). Set out to improve the efficacy and safety of immune therapies of myeloma and other haematological malignancies, the research in the haemato-oncology group is focused on three important areas: 1. Separating GvT and GvHD by: a) Identification of GvT-associated Tumor antigens and minor Histocompatibility antigens (mHag) by Genome wide genetic association analyses (GWAS) and by reverse immunology. b) Development and clinical application therapeutic dendritic cell vaccines loaded with GvT associated mHags. c) Development and clinical application adoptive immunotherapy strategies based on GvT associated mHags. d) Defining the appropriate conditions to separate GvT from GvHD using regulatory T cells. e) Development of effective cancer vaccines by protein misfolding. 2. Understanding and eliminating tumor microenvironment-related immune escape mechanisms. a) Identification, in vitro and in vivo modulation of (intra) cellular mechanisms of immune suppression and immune resistance within the bone marrow, the natural microenvironment of myeloma microenvironment. Specific attention is given to p53, Notch and WNT signalling pathways. b) identification and modulation of (intra) cellular immune suppressive/resistance mechanisms leading to extramedullar Myeloma outgrowth. 3. Development of efficient targeted antibody therapy for MM by combining novel therapeutic antibodies with immune stimulatory agents like lenalidomide, pomalidomide, bortezomib and others. The research mission of Haemato-oncology lab is strongly linked to the clinical goals of the Department of Haematology, which is one of the largest SCT centres in the Netherlands and functions as a reference centre for Multiple Myeloma (MM) patients. The preclinical research is carried out in advanced in vitro models as well as in humanized in vivo murine models that are developed with a longstanding collaboration with Dr. A.C.M. Martens. Faculty Dr. Tuna Mutis Prof. dr. Henk Lokhorst Recent publications - Groen, R.W., W.A. Noort, R.A. Raymakers, H.J. Prins, L. Aalders, F.M. Hofhuis, P. Moerer, J.F. van Velzen, A.C. Bloem, B. van Kessel, H. Rozemuller, E. van Binsbergen, A. Buijs, H. Yuan, J.D. de Bruijn, M. de Weers, P.W. Parren, J.J. Schuringa, H.M. Lokhorst, T. Mutis, and A.C. Martens (2012). Reconstructing the human hematopoietic niche in immunodeficient mice: opportunities for studying primary multiple myeloma. Blood 120, e9-e16. - Kneppers, E. B. van der Holt, M.J. Kersten, S. Zweegman, E. Meijer, G. Huls, J.J. Cornelissen, J.J. Janssen, C. Huisman, P.B. Cornelisse, C.P. Bruijnen, M. Emmelot, P. Sonneveld, H.M. Lokhorst, T. Mutis, M.C. Minnema –(2011) Lenalidomide maintenance following non-myeloablative allogeneic stem cell transplantation in multiple myeloma is not feasible: results of the HOVON 76 trial. Blood 118, 2413-2419 - Veer, M. van der, M. de Weers, B. van Kessel, J.M. Bakker, S. Wittebol, P.W.H.I. Parren, H.M. Lokhorst, T. Mutis (2011) Towards effective immunotherapy of myeloma: enhanced elimination of myeloma cells by combination of lenalidomide with the human CD38 monoclonal antibody daratumumab. Haematologica 96, 284-290

SYMPTOM DIAGNOSIS

http://www.smw.ch/content/smw-2013-13829 Review article | Published 19 September 2013, doi:10.4414/smw.2013.13829 Cite this as: Swiss Med Wkly. 2013;143:w13829 The last century of symptom-oriented research in emergency presentations – have we made any progress? Roland Bingisser, Christian Hans Nickel Emergency Department, University Hospital, Basel, Switzerland Summary This review is dedicated to the last century of symptom-oriented research, taking three symptom complexes as typical examples of medical progress, and focusing on emergency presentations. Landmark publications in each area are discussed, with an attempt to focus on the methods used to achieve major breakthroughs. In abdominal pain, progress was achieved over a century ago by correlating symptoms and surgical pathology. Most diagnoses were made by using the clinical tools elaborated with careful observation and clinical examination. Together with the later reported outcomes, surgeons had an early and powerful tool for symptom-oriented research. In dyspnoea, progress was achieved much later, as a universal definition had to be elaborated over decades by consolidating clinical research, predominantly symptom-pathology correlation, and experimental research, such as function testing and experiments with animals and humans. In nonspecific presentations in emergency situations, progress has been achieved only recently, most probably owing to the fact that elderly patients are presenting in steeply increasing numbers, and the hallmark of disease presentation in the elderly seems to be less specific symptoms and complaints. This may be caused by altered physiology, polymorbidity, polypharmacy and the multiple difficulties encountered when taking histories in the elderly. Taken together, symptom-oriented research has been an important contributor to medical progress in the last century. Though it may be challenged by image- and laboratory-oriented research, it will remain part of patient-centred research because the epidemiology of symptoms, their clinical outcomes and their diagnostic importance according to severity will be the basis for the diagnostic process.

SIEMENS: SYMBIA INTEVO

Siemens Symbia Intevo xSPECT, the difference between seeing and knowing Siemens Symbia Intevo's precise alignment of SPECT and CT enables accurate, consistent and reproducible quantification. Symbia Intevo¹ – the world's first xSPECT system – combines the high sensitivity of single-photon emission computed tomography (SPECT) with the high specificity of CT. Completely integrating data from both modalities, Symbia Intevo generates high resolution and, for the first time ever, quantitative images. Higher resolution frame of reference In conventional SPECT/CT imaging, the SPECT image has always been reconstructed using SPECT's low-fidelity frame of reference. For this reason, the CT resolution has been downgraded dramatically to the level of SPECT to enable the mechanical fusion of both datasets. Siemens' new xSPECT modality reconstructs both the SPECT and CT portions of the image using the high resolution CT frame of reference for precise, accurate alignment that facilitates the extraction and deep integration of medically relevant information. This ability is also the basis for differentiating between tissue boundaries in bone imaging. With the xSPECT Bone feature, physicians can provide additional support for detection and distinguishing between cancerous lesions and degenerative disorders. First truly quantitative SPECT Symbia Intevo's precise alignment of SPECT and CT provides physicians with essential volumetric information from the CT scan, enabling accurate, consistent and reproducible quantification – a numerical indication of a tumor's level of metabolic activity. With the xSPECT Quant feature, the physician can apply quantitative information to aid in the assessment of whether a patient's course of treatment has regressed, stabilized or grown – an assessment that is difficult to make with a purely visual assessment of the tumor. Reduced CT dose While Symbia Intevo uses more CT data than ever before, Siemens is still able to limit patient dose by offering combined applications to reduce exposure (CARE). Unique to Siemens, these applications include the CARE Dose4D technique, which can reduce patient CT radiation dose by up to 68 percent.² Increased productivity and throughput Symbia Intevo also offers applications to improve productivity and patient throughput. For example, Siemens' AUTOFORM collimator – a standard feature on Symbia Intevo – captures up to 26 percent more counts, or photons that are generated from radiotracer activity as compared to conventional collimators.² This increased number of counts potentially reduces image acquisition time for increased patient throughput. Learn more about the technology behind Symbia Intevo and the xSPECT modality here.

GRONINGEN UNIV. MULTIPLE MYELOMA (KAHLER"S DISEASE)

http://www.hematologiegroningen.nl/patienten/content/3Kahler.htm (good slides)

DAILY MAIL: GBP 6 -million for Cerebral Palsy

Legal firm IRWIN MITCHELL UK & SPAIN Location(s): Leeds Tel. 0870 1500 100 Fax. 0113 234 3322 PARTNER Rachelle Mahapatra "I have been the head of clinical negligence at the Leeds office since 1995 acting for patients in claims against doctors and hospitals. I am particularly interested in mistakes made surrounding the delivery of unborn babies causing injury sometimes serious to the baby or their mother, complications of abdominal surgery and late diagnosis of cancer. The department in Leeds covers all aspects of clinical negligence.-2421722/ Parents-schoolgirl-8-suffered-brain-damage-birth-staff-failures-win-multimillion-pound-payout.html

DAILY MAIL: HEPATITIS E

HEPATITIS E - UK: PORK SAUSAGES, ALERT ************************************** A ProMED-mail post ProMED-mail is a program of the International Society for Infectious Diseases Date: Sun 15 Sep 2013 Source: The Daily Mail, Mail-online, Health [edited] As many as one in 10 sausages is infected with a potentially deadly virus that causes liver damage, scientists warn. They are concerned that rising numbers of Britons are being struck down with hepatitis E after eating contaminated pork. The infection was once considered very rare, but cases have risen by nearly 40 per cent in a year, and there were 657 in 2012. The virus usually causes only relatively mild symptoms such as sickness, a temperature and muscle pain, which clear up by themselves within a month. But it can be fatal for the elderly, cancer victims, pregnant women and others with existing liver problems. Around one in 50 of those infected will die, rising to one in 5 pregnant women, according to statistics. Experts say sausages have to be cooked at 70 C (158 F) for at least 20 minutes to kill the virus, but they say that most Britons do not leave them in the oven for this long. Tests have showed that it can survive at 60 C after an hour. A report published last week by the Department for Environment, Food, and Rural Affairs says 10 per cent of sausages recently sampled were found to contain the virus. It states that there is increasing evidence that hepatitis E, which is common in the developing world, where it is usually transmitted through contaminated water, is a food-borne infection and adds that it is increasingly being recognised as a major disease. All forms of hepatitis cause swelling of the liver, which in severe cases can cause severe damage to the organ, liver cancer and death. More than half of those infected with hepatitis E are men over 50, who are more susceptible as they tend to drink more and their livers are weaker. The virus is particularly harmful for pregnant women who catch it in the final 3 months of their pregnancy because it can lead to acute liver failure, and one in 5 expectant mothers who catch the virus will die. Dr Harry Dalton, a consultant at the Royal Cornwall Hospital in Truro and one of Britain's leading experts on hepatitis E, said: "This is emerging as a serious problem. About 85 per cent of British pigs carry the virus, which is quite hardy. Sausages have to be cooked at 70 C for 20 minutes to kill it, and that is longer than most sausages ever get cooked. Anyone cooking with sausages or other pork products should take stringent hygiene precautions including washing their hands and cleaning work surfaces." Sausages are regarded as the most dangerous product, as they often contain liver meat and traces of pig's blood as well as a casing from the animal's intestine. -- Communicated by: ProMED-mail [The following is the DEFRA statement entitled: "Hepatitis E and detection in pork and pork products," , referred to in the above press report. "There has been recent publicity about hepatitis E infection in humans. This relates to an increase in 2010-11 in the proportion of cases of hepatitis E diagnosed where there is no history of travel by the affected person. A recent publication (Berto and others, 2012) reported PCR detection of hepatitis E virus in 13 percent of pig faeces and 3 percent of pig livers at slaughter and 10 percent of pork sausages at retail. Whether virus is infective at these different stages was not established. The report of an extensive case control study in humans is expected in 2013 and may identify risk factors and assist in determining whether there is evidence to support the putative link with consumption of pork and pork products. In the meantime, a multi-agency, joint-funded abattoir survey of pigs, expected to be conducted in early 2013, will seek to establish the prevalence of infection in slaughter pigs in the UK. This is highlighted here as an issue which may cause adverse publicity for the pig industry at what is already a difficult time." See: . Hepatitis E is a liver disease caused by hepatitis E virus: a non-enveloped, positive-sense, single-stranded ribonucleic acid virus. Hepatitis E virus is transmitted usually mainly through contaminated drinking water. It is usually a self-limiting infection and resolves within 4-6 weeks. Occasionally, a fulminant form of hepatitis develops (acute liver failure), which can lead to death. The hepatitis E virus is transmitted mainly through the faecal-oral route due to faecal contamination of drinking water. Other transmission routes have been identified, which include: foodborne transmission from ingestion of products derived from infected animals, transfusion of infected blood products, and vertical transmission from a pregnant woman to her fetus. The incubation period following exposure to the hepatitis E virus ranges from 3-8 weeks, with a mean of 40 days. The period of communicability is unknown. Typical signs and symptoms of hepatitis include: jaundice (yellow discolouration of the skin and sclera of the eyes, dark urine and pale stools, anorexia (loss of appetite), an enlarged, tender liver (hepatomegaly), abdominal pain and tenderness, nausea and vomiting. Overall population mortality rates from hepatitis E range from 0.5 to 4.0 percent. Fulminant hepatitis occurs more frequently during pregnancy. Pregnant women are at greater risk of obstetrical complications and mortality from hepatitis E, which can induce a mortality rate of 20 percent among pregnant women in their 3rd trimester. Cases of chronic hepatitis E infection have been reported in immunosuppressed people. Reactivation of hepatitis E infection has also been reported in immunocompromised people. (From: ). Previously, ProMED-mail reported cases of hepatitis E in France associated with undercooked pork sausage meat. - Mod.CP

SCOTLAND: LEGIONELLA LONGBEACHAE from compost

] Date: Fri 13 Sep 2013 Source: This Is Jersey/Jersey Evening Post [edited] A health board is investigating 4 cases of the infection [due to] _Legionella longbeachae_ linked to gardening compost. 2 patients are being treated in intensive care while 2 more have been discharged from hospital, NHS Lothian said. The 4 people affected are keen gardeners between the ages of 62 and 84. Dr Richard Othieno, NHS Lothian consultant in public health and chair of the incident management team, said: "This type of _Legionella_ is quite rare in that unlike other strains it has never been identified in man-made water systems, like cooling towers. We are working with experts to trace the source of the infection and samples of the compost have been sent for testing. We know that all of the 4 cases are keen gardeners and had purchased different products containing compost prior to acquiring the infection. Gardening is a healthy hobby but there are risks and it is important that people take some simple precautions when working in their garden or with gardening products. I would like to add further reassurance that the risk to the wider public is low." The symptoms of _Legionella longbeachae_ [infection] include headaches, diarrhoea, or a dry cough followed by pneumonia. Most people recover after treatment with antibiotics but those with underlying medical problems are more vulnerable, the health board said. It is not known exactly how the infection is passed from compost to people but health experts assume it is through breathing in very small dust particles or drops of contaminated water. The infection is not transmitted from person to person. Anyone handling garden materials such as potting mix, mulches, composts, or garden soils is advised to open bags carefully, wear gloves and keep doors to greenhouses or sheds open when potting plants or filling hanging baskets. Gardeners are also advised to wear a mask if the air is dusty, particularly indoors, and to wash their hands immediately after using compost and before smoking. There is no link between the current cases and the outbreak of [infection due to] _Legionella pneumophila_ in southwest Edinburgh in 2012, NHS Lothian said.